Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane.

Abstract:

:Despite being engineered to avoid renal clearance, many cationic polymer (polycation)-based siRNA nanoparticles that are used for systemic delivery are rapidly eliminated from the circulation. Here, we show that a component of the renal filtration barrier--the glomerular basement membrane (GBM)--can disassemble cationic cyclodextrin-containing polymer (CDP)-based siRNA nanoparticles and, thereby, facilitate their rapid elimination from circulation. Using confocal and electron microscopies, positron emission tomography, and compartment modeling, we demonstrate that siRNA nanoparticles, but not free siRNA, accumulate and disassemble in the GBM. We also confirm that the siRNA nanoparticles do not disassemble in blood plasma in vitro and in vivo. This clearance mechanism may affect any nanoparticles that assemble primarily by electrostatic interactions between cationic delivery components and anionic nucleic acids (or other therapeutic entities).

authors

Zuckerman JE,Choi CH,Han H,Davis ME

doi

10.1073/pnas.1200718109

subject

Has Abstract

pub_date

2012-02-21 00:00:00

pages

3137-42

issue

8

eissn

0027-8424

issn

1091-6490

pii

1200718109

journal_volume

109

pub_type

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